In silico ADMET, molecular docking and molecular simulation-based study of glabridin’s natural and semisynthetic derivatives as potential tyrosinase inhibitors

Hyper-pigmentation conditions may develop due to erroneous melanogenesis cascade which leads to excess melanin production. Recently, inhibition of tyrosinase is the main focus of investigation as it majorly contributes to melanin production. This inhibition property can be exploited in medicine, agriculture, and in cosmetics. Present study aims to find a natural and safe alternative molecule as tyrosinase inhibitor. In this study, human tyrosinase enzyme was modelled due to unavailability of its crystal structure to look into the degree of efficacy of glabridin and its 15 derivatives as tyrosinase inhibitor. Docking was performed by Autodock Vina at the catalytic core enzyme. Glabridin effects on melanoma cell lines was also elucidated by analysing cytotoxicity and effect on melanin production. Computational ADME analysis was done by SwissADME. Molecular dynamic simulation was also performed to further evaluate the interaction profile of these molecules and kojic acid (positive inhibitor) with respect to apo protein. Notably, four derivatives 5′-formylglabridin, glabridin dimer, 5′-prenyl glabridin and R-glabridin exhibited better binding affinity than glabridin. Glabridin effectively inhibited melanin production in a dose dependent manner. Among these, 5′-formylglabridin displayed highest binding affinity with docking score − 9.2 kcal/mol. Molecular properties and bioactivity analysis by Molinspiration web server and by SwissADME also presented these molecules as potential drug candidates. The study explores the understanding for the development of suitable tyrosinase inhibitor/s for the prevention of hyperpigmentation. However, a detailed in vivo study is required for glabridin derivatives to suggest these molecules as anti-melanogenic compound. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13596-022-00640-8.